吡非尼酮对于特发性肺纤维化的疗效及不良反应的Meta分析

中华养生保健 ›› 2023, Vol. 41 ›› Issue (16): 65-70.

吡非尼酮对于特发性肺纤维化的疗效及不良反应的Meta分析

杨坚^1,2, 罗倩倩³, 李涛⁴, 王泽宁⁵, 王寿寿^1,2, 江占世^1,2, 刘书盈^1,2, 董九伟^6,7,*

1.滨州医学院烟台附属医院呼吸与危重症医学科,山东烟台,264100;
2.滨州医学院第二临床医学院,山东烟台,264003;
3.滨州医学院护理学院,山东烟台,264003;
4.滨州医学院医学影像学院,山东烟台,264003;
5.滨州医学院第一临床医学院,山东烟台,264003;
6.烟台市芝罘区妇幼保健院儿科,山东烟台,264000;
7.中国人民解放军联勤保障部队第970医院儿科,山东烟台,264000

出版日期:2023-08-16 发布日期:2023-08-08
通讯作者: ^*董九伟,E-mail: dongjw107@163.com。
作者简介:杨坚（1984—）,男,汉族,籍贯：山东省烟台市,博士研究生,主治医师,研究方向：间质性肺疾病的临床与基础研究。
基金资助:
山东省医药卫生科技发展计划（202003021204）; 山东省医学会科研专项资金（YXH2022ZX02033）; 滨州医学院教学改革与研究面上项目（JYKTMS2021019）; 滨州医学院烟台附属医院课程思政专项资助项目（2021JGKTZ02）

Meta-Analysis on Efficacy and Adverse Reactions of Pirfenidone in Idiopathic Pulmonary Fibrosis

YANG Jian^1,2, LUO Qian-qian³, LI Tao⁴, WANG Ze-ning⁵, WANG Shou-shou^1,2, JIANG Zhan-shi^1,2, LIU Shu-ying^1,2, DONG Jiu-wei^6,7,*

1. Respiratory and Critical Care Medicine, Yantai Affiliated Hospital of Binzhou Medical University Yantai Shandong, 264100, China;
2. Second Clinical Medical College of Binzhou Medical University, Yantai Shandong, 264003, China;
3. Nursing College of Binzhou Medical University,Yantai Shandong, 264003, China;
4. Medical Imaging College of Binzhou Medical University, Yantai Shandong, 264003, China;
5. The First Clinical Medical College of Binzhou Medical University , Yantai Shandong, 264003, China;
6. Department of pediatrics of Yantai Zhifu District Maternal and Child Health Care Hospital, Yantai Shandong, 264000, China;
7. Department of pediatrics of the 970th Hospital of the PLA Joint Logistic Support Force, Yantai Shandong, 264000, China

Online:2023-08-16 Published:2023-08-08

摘要/Abstract

摘要： 目的系统评价吡非尼酮对特发性肺纤维化（IPF）的疗效及不良反应。方法在Pubmed、Web Of Science、CNKI、万方、维普检索1999年—2022年发表的以吡非尼酮为干预措施治疗IPF的随机对照试验。按Cochrane系统评价方法,评价纳入研究的方法学质量并进行统计分析,采用RevMan5.3进行Meta分析。结果最终纳入13篇文献,合计2 088例病例。Meta分析结果表示,与对照组相比,吡非尼酮组的肺功能主要指标用力肺活量（FVC）的改善程度明显高于对照组,差异有统计学意义[SMD=1.03,95%CI（0.81,1.24）,P<0.001],第一秒用力肺活量（FEV₁）的改变[SMD=0.96,95%CI（0.77,1.16）,P<0.001]、一氧化碳弥散量（DLCO）的改变[SMD=0.30,95%CI（0.09,0.51）,P=0.005]、PaO₂的改变[SMD=0.57,95%CI（0.28,0.86）,P<0.001]等次要指标比较,差异有统计学意义（P<0.05）;吡非尼酮组的皮疹[RR=2.81,95%CI（2.17,3.65）,P<0.001]、头晕[RR=1.59,95%CI（1.21,2.09）,P<0.001]、胃肠道反应[RR=1.87,95%CI（1.65,2.12）,P<0.001]等不良反应发生率与对照组比较,差异有统计学意义（P<0.05）。结论吡非尼酮能有效延缓IPF患者的肺功能恶化,用药后出现的不良反应多为皮疹、头晕及胃肠道不良反应等,但不良反应较轻,患者可耐受。

关键词: 吡非尼酮, 特发性肺纤维化, 疗效, 不良反应, Meta分析

Abstract: Objective To systematically assess the efficacy and adverse reactions of pirfenidone in patients with idiopathic pulmonary fibrosis (IPF) by meta-analysis. Methods Randomized controlled trials using pirfenidone as an intervention to treat IPF published from 1999 to 2022 were searched in PubmedWeb Of Science, CNKI, WanFang database and VIP database. Methodological quality evaluation and statistical analysis were conducted using Review Manager 5.3 provided by the Cochrane Collaboration. Results 13 clinical trials,involving 2088 patients, met the inclusion. The improvement of forced vital capacity (FVC), the main index of lung function, was significantly higher in pirfenidone group than in control group[SMD=1.03, 95%CI (0.81, 1.24), P<0.001]. And most of the secondary indexes, such as the change of FEV₁ [SMD=0.96,95%CI (0.77, 1.16),P<0.001], the change of DLCO[SMD=0.30, 95%CI (0.09, 0.51, P=0.005]and the change of PaO₂[SMD=0.57, 95%CI (0.28,0.86), P<0.001], were statistically significant; the incidence of rash between pirfenidone group and control group was statistically significant[RR=2.81, 95%CI (2.17, 3.65), P<0.001]. The incidence of adverse reactions including dizziness [RR=1.59, 95%CI (1.21,2.09), P<0.001], gastrointestinal reaction [RR=1.87,95%CI (1.65,2.12), P<0.001] were compared with the control group. Conclusion Pirfenidone can delay the decline of pulmonary function in patients with idiopathic pulmonary interstitial fibrosis and slow the progression of the disease. Adverse reactions are common, and they are mild and can be tolerated by patients.

Key words: pirfenidone, IPF, efficacy, adverse reaction, meta-analysis

中图分类号:

R563

杨坚, 罗倩倩, 李涛, 王泽宁, 王寿寿, 江占世, 刘书盈, 董九伟. 吡非尼酮对于特发性肺纤维化的疗效及不良反应的Meta分析[J]. 中华养生保健, 2023, 41(16): 65-70.

YANG Jian, LUO Qian-qian, LI Tao, WANG Ze-ning, WANG Shou-shou, JIANG Zhan-shi, LIU Shu-ying, DONG Jiu-wei. Meta-Analysis on Efficacy and Adverse Reactions of Pirfenidone in Idiopathic Pulmonary Fibrosis[J]. ZHONGHUA YANGSHENG BAOJIAN, 2023, 41(16): 65-70.

参考文献

[1] 王粉利,付伟,李健,等.吡非尼酮治疗特发性肺纤维化的临床效果[J].临床医学研究与实践,2019,4(9):32-34.
[2] 陈红艳,郭淑敏,何梅.间歇性肺康复训练对特异性肺纤维化患者运动能力及生命质量的影响[J].中国药物与临床,2019,19(4):546-549.
[3] 刘寅,蔡后荣.特发性肺纤维化的HRCT诊断新观点[J].中国临床新医学,2019,12(1):13-17.
[4] 雷凯春,岳红梅,周婷婷.吡非尼酮治疗特发性肺纤维化的临床疗效及不良反应[J].中国新药与临床杂志,2018,37(3):160-163.
[5] 王雪,李巧玲,高云云,等.吡非尼酮联合尼达尼布治疗小鼠肺纤维化的效果[J].中国当代医药,2019,26(9):38-40.
[6] RAGHU G, ROCHWERG B, ZHANG Y, et al.An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline: Treatment of Idiopathic Pulmonary Fibrosis. An Update of the 2011 Clinical Practice Guideline[J]. Am J Respir Crit Care Med,2015,192(2):e3-e19.
[7] 耿艳艳,周植星,胡倩倩,等.特发性肺纤维化治疗靶点及药物研究进展[J].中国新药杂志,2015,24(1):46-51.
[8] 王春彬,张爽,张倩,等.两种新型抗纤维化药物治疗特发性肺纤维化的研究进展[J].中国药学杂志,2019,54(9):682-686.
[9] 曾宪涛,包翠萍,曹世义,等.Meta分析系列之三:随机对照试验的质量评价工具[J].中国循证心血管医学杂志,2012,4(3):183-185.
[10] HUANG H, DAI H P, KANG J, et al.Double-Blind Randomized Trial of Pirfenidone in Chinese Idiopathic Pulmonary Fibrosis Patients[J]. Medicine (Baltimore),2015,94(42):e1600.
[11] GAHL W A, BRANTLY M, TROENDLE J, et al.Effect of pirfenidone on the pulmonary fibrosis of Hermansky-Pudlak syndrome[J]. Mol Genet Metab,2002,76(3):234-242.
[12] O’BRIEN K, TROENDLE J, GOCHUICO B R,et al. Pirfenidone for the treatment of Hermansky-Pudlak syndrome pulmonary fibrosis[J]. Mol Genet Metab,2011,103(2):128-134.
[13] NOBLE P W, ALBERA C, BRADFORD W Z, et al.Pirfenidone in patients with idiopathic pulmonary fibrosis (CAPACITY): two randomised trials[J]. Lancet,2011,377(9779):1760-1769.
[14] 董燕,陈俊文,王业亚,等.吡非尼酮治疗COPD并发肺纤维化的临床疗效观察[J].西部医学,2019,31(9):1426-1431.
[15] 李云霞,李琼,加慧,等.吡非尼酮治疗特发性肺纤维化的临床研究[J].航空航天医学杂志,2016,27(11):1365-1367.
[16] 史广超,刘鑫,杨小静,等.吡非尼酮治疗特发性肺纤维化患者的临床疗效及对肺功能的影响[J].临床肺科杂志,2018,23(10):1838-1841.
[17] 李惠萍,王思勤,周建英,等.国产吡非尼酮治疗特发性肺纤维化Ⅱ期临床研究[J].中国呼吸与危重监护杂志,2015,14(3):229-235.
[18] KING T J, BRADFORD W Z, CASTRO-BERNARDINI S, et al.A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis[J]. N Engl J Med,2014,370(22):2083-2092.
[19] AZUMA A, NUKIWA T, TSUBOI E, et al.Double-blind, placebo-controlled trial of pirfenidone in patients with idiopathic pulmonary fibrosis[J]. Am J Respir Crit Care Med,2005,171(9):1040-1047.
[20] TANIGUCHI H, EBINA M, KONDOH Y, et al.Pirfenidone in idiopathic pulmonary fibrosis[J]. Eur Respir J,2010,35(4):821-829.
[21] ARAVENA C, LABARCA G, VENEGAS C, et al.Correction: Pirfenidone for Idiopathic Pulmonary Fibrosis: A Systematic Review and Meta-Analysis[J]. PLoS One,2015,10(10):e140288.
[22] SKOLD C M, BENDSTRUP E, MYLLARNIEMI M, et al.Treatment of idiopathic pulmonary fibrosis: a position paper from a Nordic expert group[J]. J Intern Med,2017,281(2):149-166.